1. Field of the Invention
This invention relates to a process for the optical resolution of an optically inactive (.+-.)-cis-4-aminocyclopent-2-en-1-carboxylic acid represented by Formula (1) (hereinafter abbreviated "(.+-.)ACP acid") into its optically active (+)ACP acid derivative and (-)ACP acid derivative. ##STR1## wherein R represents an acyl group.
2. Description of the Related Art
In recent years, there is a world-wide problem of an increase in persons infected with AIDS (aquired immune deficiency syndrome) viruses, and it has been attempted to remedy AIDS infections by various methods. Under such circumstances, an optically active isomer of a compound commonly called a carbovir, represented by Formula (2): ##STR2## has attracted notice because of its inhibitory action against the proliferation of AIDS viruses.
Thus, it is attempted to synthesize the optically active carbovir of Formula (2). For example, it is proposed to use a chiral natural product, aristeromycin, as a starting material (C. Willamson, A. M. Exall et al., Poster Presentation at SCI Medical Chemistry Symposium, Cambridge, 1989). This method, however, has the problem that the chiral natural product as a starting material is available with so great a difficulty and is so expensive that the carbovir can not be produced in an industrial scale and at a low cost.
For this reason, it is attempted to chemically synthesize the carbovir of Formula (2) without using as a starting material the natural product available with difficulty (J. Chem. Soc., Chem. Commun., 1120(1990); J. Chem. Soc., Perkin Trans., 1, 2479(1990); and J. Chem. Soc., Perkin Trans., 1, 589(1992). An important subject in the chemical synthesis of such a carbovir is for one thing how an optically active (-)-4-hydroxymethyl-2cyclopentenyl group is introduced into the main skeleton of the carbovir of Formula (2).
As one of conventional reliable means for settling this subject, it is proposed to use a synthesis method in which optically active (-)-4-N-acetylamino-1-hydroxymethyl-2-cyclopentene of Formula (3) which is a compound corresponding to the (-)-4-hydroxymethyl-2-cyclopentenyl group is allowed to react with 2-amino-4,6-dichloropyridine of Formula (4) to produce (-)-4-hydroxymethyl-4-[(2'-amino-6'-chloropyrimidin-4'-yl)amino]-2-cyclope ntene of Formula (5), as shown below [J. Chem. Soc., Chem. Commun., 1120(1990)]. ##STR3##
In this case, the compound of Formula (3) is synthesized by subjecting optically inactive 2-azabicyclo[2.2.1]hept-5-en-3-one to optical resolution in the presence of a whole cell catalyst to obtain optically active (-)-2-azabicyclo[2.2.1]hept-5-en-3-one, subjecting this isomer to hydrolysis to obtain an optically active ACP acid as an intermediate material and further subjecting this acid to esterification reaction, acetylation reaction and reduction reaction.
However, the method making use of the whole cell catalyst as mentioned above requires a reasonably long time for the optical resolution in order to obtain the optically active ACP acid, and has been involved in the problem that it is not suited for large-scale treatment and the compound can not be produced in an industrial scale and at a low cost.